Medical Treatment of Cushing's Disease
Medical Treatment of Cushing's Disease
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DOI：
10.1210/jc.2012-3126
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发表时间：
2013-02-01
影响因子：
5.8
通讯作者：
Hofland, Leo J.
中科院分区：
文献类型：
--
作者：
Feelders, Richard A.;Hofland, Leo J.
背景：库欣病（CD）与严重的发病率相关，如果治疗不理想，死亡率会增加。虽然手术是乳糜泻的一线治疗方式，但高皮质醇血症在一个重要的患者亚群中持续存在或复发。考虑到不受控制的乳糜泻的有害影响，显然需要有效的药物治疗。目的：在这篇综述中，我们讨论了药物治疗的分子靶点，目前使用的药物治疗高皮质醇症的疗效和副作用，并重点介绍了转化和临床研究的最新进展。证据获取：通过使用相关关键词和搜索词在PubMed上进行搜索，选择与研究目标相关的出版物。主要发现：药物治疗可分为垂体导向、肾上腺阻断和糖皮质激素受体拮抗剂。最近的研究表明，生长抑素受体亚型5 （sst(5)）和多巴胺受体亚型2 （D-2）在促皮质腺瘤中经常（共）表达。分别针对sst(5)和D-2的pasireotide和卡麦角林垂体靶向治疗在大约25-30%的患者中是成功的。肾上腺素阻断药物可通过抑制类固醇酶活性而有效。最后，糖皮质激素受体拮抗剂米非司酮在大多数患者中诱导临床和代谢改善。每种药物都有严重的副作用，可能会影响长期治疗。一般来说，中度至重度高皮质醇症患者需要联合治疗以使皮质醇的产生正常化。结论：乳糜泻的药物治疗可有不同程度的针对性，应因地制宜。未来的研究应该检查CD的最佳剂量和药物治疗方式的组合。[J]临床内分泌杂志，1998:425-438,2013。
Context: Cushing's disease (CD) is associated with serious morbidity and, when suboptimally treated, an increased mortality. Although surgery is the first-line treatment modality for CD, hypercortisolism persists or recurs in an important subset of patients. Considering the deleterious effects of uncontrolled CD, there is a clear need for effective medical therapy.Objective: In this review, wediscuss molecular targets for medical therapy, efficacy, and side effects of the currently used drugs to treat hypercortisolism and focus on recent developments resulting from translational and clinical studies.Evidence Acquisition: Selection of publications related to the study objective was performed via a PubMed search using relevant keywords and search terms.Main Findings: Medical therapy for CD can be classified into pituitary-directed, adrenal-blocking, and glucocorticoid receptor-antagonizing drugs. Recent studies demonstrate that somatostatin receptor subtype 5 (sst(5)) and dopamine receptor subtype 2 (D-2) are frequently (co-) expressed by corticotroph adenomas. Pituitary-directed therapy with pasireotide and cabergoline, targeting sst(5) and D-2, respectively, is successful in approximately 25-30% of patients. Adrenal-blocking drugs can be effective by inhibiting steroidogenic enzyme activity. Finally, the glucocorticoid receptor antagonist mifepristone induces clinical and metabolic improvement in the majority of patients. Each drug can have important side effects that may impair long-term treatment. Generally, patients with moderate to severe hypercortisolism need combination therapy to normalize cortisol production.Conclusion: Medical therapy for CD can be targeted at different levels and should be tailored in each individual patient. Future studies should examine the optimal dose and combination of medical treatment modalities for CD. (J Clin Endocrinol Metab 98: 425-438, 2013)